Molecular and Cellular Oncology Research Program

项目摘要/摘要 分子和细胞肿瘤学(MCO)研究计划的目标是获得全面的 了解肿瘤发生、发展、转移和治疗的基本机制 抵抗，以促进癌症预防和治疗的新的和合理的方法的发展。MCO 研究工作是马基癌症中心(MCC)减轻癌症负担的整体使命的核心 重点关注肯塔基州及其最脆弱的人群，通过研究、预防、治疗、 教育和社区参与。MCO调查人员确定信号、遗传、表观遗传和 促进癌症发展、推动肿瘤进展并有助于治疗的代谢机制 抵抗。为了实现其目标，MCO提出了三个相互关联的目标：1)识别异常信令网络 以及肿瘤细胞与其微环境的关键相互作用，以描述 推动肿瘤的发生、发展、转移和耐药；2)决定代谢的贡献 重新编程和表观遗传失调以确定促进癌细胞存活和 适应；3)描述氧化还原信号的失调促进基因组的机制 不稳定，治疗耐药和正常的组织毒性。MCO计划的54名成员都是专家 癌细胞信号、肿瘤微环境、癌症代谢、表观遗传调控和氧化还原生物学 他们来自医学院、工程学院、文理学院和农业学院的16个系， 食品和环境，反映了不同的学科观点。与癌症相关的MCO资金几乎 每年1030万美元的直接成本，MCO同行审查资金的53%来自NCI。成员们有 发表320篇稿件(2018年7月-2022年6月)，其中106篇(33%)是跨计划的，81篇(25%)是 方案内，195个(61%)是机构间的。该项目由三名研究人员共同领导， 在三个方案领域中的每一个领域都有专门知识。Rina Plattner博士(致癌信号转导专家 和肿瘤转移)，周彬华博士(表观遗传和代谢重新编程的专家 上皮-间充质转化)和高天燕博士(蛋白质磷酸酶和线粒体专家 癌症干细胞的调控)汇集了癌症信号传递(Plattner，Aim 1)、表观遗传学和 代谢(周，目标2)和氧化还原生物学和线粒体生物能量学(高，目标3)。除了他们的 科学领导力，每个人都在临床翻译、初级教员指导、 MCC研究计划和MCC流域内人口的专业知识之间的交流 区域。通过利用综合计划的优势，MCO计划共同提供了丰富的 促进多学科协作的环境，并为MCO的翻译建立富有成效的渠道 把科学带入临床。

PROJECT SUMMARY/ABSTRACT The goal of the Molecular and Cellular Oncology (MCO) Research Program is to gain a comprehensive understanding of basic mechanisms driving cancer initiation, progression, metastasis and therapeutic resistance to facilitate development of novel and rational approaches for cancer prevention and therapy. MCO research efforts are central to the overall Markey Cancer Center (MCC) mission to reduce the cancer burden with a focus on Kentucky and its most vulnerable populations through research, prevention, treatment, education and community engagement. MCO investigators determine signaling, genetic, epigenetic and metabolic mechanisms that promote cancer development, fuel tumor progression and contribute to therapeutic resistance. To achieve its goal, MCO proposes three inter-related aims: 1) Identify aberrant signaling networks and critical interactions of tumor cells with their microenvironment to delineate molecular mechanisms that drive tumor initiation, progression and metastasis and resistance; 2) Determine the contribution of metabolic reprogramming and epigenetic dysregulation to define novel pathways promoting cancer cell survival and adaptation; 3) Delineate the mechanisms by which dysregulation of redox signaling promotes genomic instability, therapeutic resistance and normal tissue toxicity. The 54 members of the MCO Program are experts in cancer cell signaling, tumor microenvironment, cancer metabolism, epigenetic regulation and redox biology who hail from 16 departments in the Colleges of Medicine; Engineering; Arts and Sciences; and Agriculture, Food and Environment, reflecting diverse disciplinary perspectives. Cancer-related MCO funding is nearly $10.3M in annual direct costs, and 53% of MCO peer-reviewed funding is from the NCI. Members have published 320 manuscripts (July 2018–June 2022), of which 106 (33%) are inter-programmatic, 81 (25%) are intra-programmatic, and 195 (61%) are inter-institutional. The program is co-led by three researchers with expertise in each of the three programmatic areas. Dr. Rina Plattner (an expert in oncogenic kinase signaling and tumor metastasis), Dr. Binhua “Peter” Zhou (a specialist in epigenetic and metabolic reprogramming of epithelial-mesenchymal transition) and Dr. Tianyan Gao (an expert in protein phosphatases and mitochondrial regulation of cancer stem cells) bring together expertise in cancer signaling (Plattner, Aim 1), epigenetics and metabolism (Zhou, Aim 2) and redox biology and mitochondrial bioenergetics (Gao, Aim 3). In addition to their scientific leadership, each offers significant strengths in clinical translation, junior faculty mentoring, communications among MCC Research Programs and expertise on populations within the MCC catchment area. By leveraging comprehensive program strengths, the MCO Program collectively provides a rich environment to facilitate multidisciplinary collaboration and builds a productive pipeline for translation of MCO science into the clinic.